精准医学杂志 (Jun 2024)
Effect of indoxyl sulfate on myocardial remodeling in a mouse model of myocardial infarction
Abstract
Objective To investigate the effect of indoxyl sulfate (IS) on myocardial remodeling in a mouse model of myocardial infarction (MI). Methods A total of 50 adult male C57BL/6J mice were randomly divided into sham-operation group (Sham group) with 10 mice, sham operation+indoxyl sulfate group (Sham+IS group) with 10 mice, myocardial infarction group (MI group) with 15 mice, and myocardial infarction+indoxyl sulfate group (MI+IS group) with 15 mice. Left anterior descending coronary artery ligation was performed to establish a mouse model of MI, and at 24 hours after surgery, the mice in the Sham+IS group and the MI+IS group were given intraperitoneal injection of IS (100 mg/kg), while those in the Sham group and the MI group were given intraperitoneal injection of an equal volume of PBS, once a day for 28 consecutive days. The survival status of the mice in each group was recorded during this period of time. On day 30 of the experiment, echocardiography was performed to evaluate the cardiac function of mice in each group. Ultra-performance liquid chromatography was used to measure the serum concentration of IS. Masson staining was used to assess the degree of myocardial fibrosis in the infarct zone. RT-qPCR was used to measure the mRNA expression levels of α-sma and Collagen Ⅰ in myocardial tissue. Western blot was used to measure the protein expression levels of the TGF-β signaling pathway marker proteins TGF-β, p-Smad2, and p-Smad3 in myocardial tissue. Results On day 30 of the experiment, the MI+IS group had a significant reduction in the survival rate of mice compared with the MI group (χ2=5.02,P<0.05). Compared with the Sham group, the Sham+IS group had a significant increase in the serum concentration of IS (t=54.87,P<0.05), and compared with the MI group, the MI+IS group had a significant increase in the serum concentration of IS (t=38.55,P<0.05). Echocardiography showed no significant differences between the Sham group and the Sham+IS group in left ventricular internal diameter at end-diastole (LVIDd), left ventricular internal diameter at end-systole (LVIDs), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) (P>0.05). Compared with the MI group, the MI+IS group had significant increases in LVIDd and LVIDs (t=3.96,4.31,P<0.05) and significant reductions in LVEF and LVFS (t=5.68,4.07,P<0.05). Masson staining showed that compared with the MI group, the MI+IS group had a significant increase in interstitial collagen fiber deposition. RT-qPCR showed that compared with the MI group, the MI+IS group had significant increases in the mRNA expression levels of α-sma and Collagen Ⅰ in myocardial tissue (t=8.74,4.78,P<0.05). Western blot showed that compared with the MI group, the MI+IS group had significant increases in the protein expression levels of TGF-β, p-Smad2, and p-Smad3 in myocardial tissue (t=4.04-5.64,P<0.05). Conclusion IS can aggravate pathological myocardial remodeling in mice with MI, possibly by activating the TGF-β signaling pathway.
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